Newborn infants of mothers with diabetes mellitus have a higher incidence of the respiratory distress syndrome (RDS) than infants of nondiabetics. Delayed fetal lung maturation is one of several mechanisms proposed to explain this association; as envisioned, the delay is due to the metabolic effects of maternal diabetes on the fetus and leads to inadequate development of the pulmonary surfactant system. The overall goal of this project is to examine the process of fetal lung development in the diabetic pregnancy and determine why infants of diabetic mothers are especially susceptible to RDS. Specific objectives are: 1) to delineate the complete phospholipid composition of amniotic fluid (AF) throughout the third trimester in diabetics, as an indicator of fetal lung development; 2) to devise an approach to AF phospholipid analysis which will permit accurate assessment of the lung, such that the risk of RDS in infants of diabetic mothers can be ascertained prenatally; and 3) to utilize the Rhesus monkey model of diabetes for comparative studies in which AF phospholipids will be examined and a direct investigation of fetal lung biochemistry and physiology will be conducted during late gestation. Amniocenteses have been performed on diabetic and non-diabetic pregnant women. Lipids are extracted from amniotic fluid samples for measurement of total lecithin, sphingomyelin, phosphatidylglycerol, phosphatidylinositol, and phosphatidylserine. The fatty acid composition of the foregoing phospholipids is then determined by gas chromatography. A new method for measurement of disaturated lecithin is being devised and adapted for routine clinical use to assess the reliability of this determination and the above battery of phospholipids in predicting fetal lung maturation. Glucose intolerance has been induced in female Rhesus monkeys by streptozotocin infusion to create an experimental model of diabetes mellitus. Fetal lung development is being studied by a multidisciplinary approach designed to examine in detail the biochemical and physiologic processes of pulmonary maturation.